Prader-Willi and Angelman syndromes — formative SAQs

SAQ 1 (10 marks)

A two-week-old neonate is referred for profound hypotonia, poor feeding, and a weak cry. Birth weight was at the 10th centile. He requires nasogastric feeding. Examination reveals a narrow bifrontal diameter, almond-shaped palpebral fissures, a thin upper lip, bilateral cryptorchidism, and acromicria. A standard karyotype has been reported as normal. ^{[1] [3]}

a) Give the most likely diagnosis and explain why a normal karyotype does not exclude it. Name the first-tier molecular test you will order. (3 marks) ^{[1] [4]}

b) Describe the three molecular subtypes of this syndrome, their approximate relative frequencies, and the mechanism by which each produces the phenotype. (3 marks) ^{[3] [4]}

c) Outline the syndrome-specific management plan for this child across infancy and childhood, naming four domains that require active intervention. (2 marks) ^{[1] [7]}

d) Explain why molecular subtype determination is essential for genetic counselling, and state the recurrence risk for each subtype. (2 marks) ^[4]